期刊
CLINICAL LUNG CANCER
卷 11, 期 4, 页码 223-227出版社
CIG MEDIA GROUP, LP
DOI: 10.3816/CLC.2010.n.028
关键词
Autocrine growth pathway; c-Kit inhibitor; Stem cell factor; Tyrosine kinase
类别
Background: The prognosis for patients with extensive-stage small-cell lung cancer remains poor. This trial was designed to evaluate irinotecan/cisplatin plus maintenance imatinib in patients with c-Kit positive disease (the transmembrane receptor c-Kit is the product of the c-KIT protooncogene). Patients and Methods: Immunohistochemistry for c-Kit was performed before enrollment Treatment consisted of irinotecan 65 mg/m(2) on days 1 and 8 plus cisplatin 60 mg/m(2) on day 1 and every 21 days for 4 cycles. Imatinib was administered at 400 mg twice a day until progression or unacceptable toxicity occurred Results: Fourteen patients were enrolled. Slow accrual led to early study termination Six patients did not begin treatment with imatinib because of disease progression, persistent toxicity, or referral for radiation therapy. Eight patients had a partial response with irinotecan/cisplatin and received imatinib The median number of weeks on imatinib was 6.1 (range, 4 1-25.1 weeks). Reasons for imatinib discontinuation included disease progression (n = 7) and persistent neutropenia (n = 1) No objective responses to imatinib were evident, but 3 patients (21%) exhibited stable disease for 12, 15, and 25 weeks The median progression-free survival was 43 months (95% CI, 2 9-4 8 months) The median overall survival was 7 8 months (95% CI, 5 7-10 0 months). The irinotecan/cisplatin regimen was well tolerated (grade 1/2 neutropenia, 29%, anemia, 43%, thrombocytopenia, 14%, and diarrhea, 29%), except in 1 patient with grade 3 vomiting. Imatinib toxicity included grade 1/2 nausea in 50% of the patients, peripheral edema in 75% of the patients, grade 3 fatigue in 13% of the patients, and neutropenia in 13% of the patients. Conclusion: Despite the selection of tumors expressing c-Kit, imatinib did not appear to delay disease progression after response to chemotherapy However, this trial was underpowered because of its early termination. Although disease stability with imatinib was evident in 3 patients and the therapy was well tolerated, this approach does not appear to warrant further clinical study.
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